Vinculin Regulates Assembly of Talin: β3 Integrin Complexes

Nanda, Suman Yadav; Hoang, Thuy; Patel, Priya; Zhang, Hao

doi:10.1002/jcb.24772

Cited by 13 publications

(6 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vinculin present in focal adhesions may be tightly bound to ACTN1 and other proteins, and therefore not available for binding with peptide. Since vinculin has roles in both integrin activation and inhibition[14], the co-localization of peptide with vinculin seen here could be consistent with a damping of its potential inhibitory effects, but may act through a number of potential mechanisms.…”

Section: Resultssupporting

confidence: 67%

“…Adhesome proteins that are embryonic lethal (see S1 Table) tend to have many interactors (i.e. are “hub” proteins, such as integrin, paxillin, Grb2 and FAK), while those with fewer interactors such as tensin, vimentin and IAP have less deleterious consequences [8][14]. Knockout of the highly connected Src is not lethal, perhaps because of compensation by the homologous kinases Lyn and Fyn[8].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Computational and experimental analysis of bioactive peptide linear motifs in the integrin adhesome

et al. 2019

View full text Add to dashboard Cite

Therapeutic modulation of protein interactions is challenging, but short linear motifs (SLiMs) represent potential targets. Focal adhesions play a central role in adhesion by linking cells to the extracellular matrix. Integrins are central to this process, and many other intracellular proteins are components of the integrin adhesome. We applied a peptide network targeting approach to explore the intracellular modulation of integrin function in platelets. Firstly, we computed a platelet-relevant integrin adhesome, inferred via homology of known platelet proteins to adhesome components. We then computationally selected peptides from the set of platelet integrin adhesome cytoplasmic and membrane adjacent protein-protein interfaces. Motifs of interest in the intracellular component of the platelet integrin adhesome were identified using a predictor of SLiMs based on analysis of protein primary amino acid sequences (SLiMPred), a predictor of strongly conserved motifs within disordered protein regions (SLiMPrints), and information from the literature regarding protein interactions in the complex. We then synthesized peptides incorporating these motifs combined with cell penetrating factors (tat peptide and palmitylation for cytoplasmic and membrane proteins respectively). We tested for the platelet activating effects of the peptides, as well as their abilities to inhibit activation. Bioactivity testing revealed a number of peptides that modulated platelet function, including those derived from α-actinin (ACTN1) and syndecan (SDC4), binding to vinculin and syntenin respectively. Both chimeric peptide experiments and peptide combination experiments failed to identify strong effects, perhaps characterizing the adhesome as relatively robust against within-adhesome synergistic perturbation. We investigated in more detail peptides targeting vinculin. Combined experimental and computational evidence suggested a model in which the positively charged tat-derived cell penetrating part of the peptide contributes to bioactivity via stabilizing charge interactions with a region of the ACTN1 negatively charged surface. We conclude that some interactions in the integrin adhesome appear to be capable of modulation by short peptides, and may aid in the identification and characterization of target sites within the complex that may be useful for therapeutic modulation.

show abstract

Section: Resultssupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Computational and experimental analysis of bioactive peptide linear motifs in the integrin adhesome

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Integrins as transmembrane proteins have the function of connecting the cytoskeleton and modulating intracellular signals, with respect to the cell adhesion . Integrins are αβ heterodimeric, and integrin β1 is the most ubiquitously expressed subunit, which links with a number of subunits, resulting in diverse functions . In recent years, integrin β3 has entered our line of sight.…”

Section: Discussionmentioning

confidence: 99%

Microenvironmental Stiffness Regulates Dental Papilla Cell Differentiation: Implications for the Importance of Fibronectin–Paxillin−β-Catenin Axis

Bai

Xie

Liu

et al. 2018

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

The mechanical stiffness of substrates is recognized to be an important physical cue in the microenvironment of local cellular residents in mammalian species due to their great capacity in regulating cell behavior. Dental papilla cells (DPCs) play an important role in the field of dental tissue engineering for their stem cell-like properties. Therefore, it is essential to provide the suitable microenvironment by combining with the physical cues of biomaterials for DPCs to carry out the function of effective tissue regeneration. However, how the substrate stiffness influences the odontogenic differentiation of DPCs is still unclear. Thus, we fabricated poly(dimethylsiloxane) substrates with varied stiffness for cell behavior. Both cell morphology and focal adhesion were shown to have significant changes in response to varied stiffness. Paxillin, an important protein adapter of focal adhesion kinase protein, was shown to interact with both ectoplasmic fibronectin and cytoplasmic β-catenin by coimmunoprecipitation. The resultant changes of β-catenin by varied stiffness were confirmed by immunofluorescent stain and western blotting. Further, the higher quantity nuclear translocation of β-catenin and the less phospho-β-catenin on the stiff substrate were detected. This nuclear translocation in the stiff substrate finally led to an increased mineralization of DPCs relative to the soft substrate detected by Von Kossa and Alizarin Red stain. Taken together, this work not only points out that the substrate stiffness can regulate the odontogenic differentiation potential of DPCs via fibronectin/paxillin/β-catenin pathway but also provides significant consequence for biomechanical control of cell behavior in cell-based tooth tissue regeneration.

show abstract

“…The recruitment of vinculin to talin stabilizes focal adhesions and promotes integrin clustering and enlargement [38, 39]. More recent work shows vinculin directly regulates integrin activation through talin [39–41]. Investigations into how this occurs suggest when a cell signals for increased integrin activation, talin is redistributed from the cytoplasm to the plasma membrane.…”

Section: Vinculin In Cell–matrix Adhesionsmentioning

confidence: 99%

Vinculin in cell–cell and cell–matrix adhesions

Bays

DeMali

2017

Cell. Mol. Life Sci.

374

295

View full text Add to dashboard Cite

Vinculin was identified as a component of focal adhesions and adherens junctions nearly 40 years ago. Since that time, remarkable progress has been made in understanding its activation, regulation and function. Here we discuss the current understanding of the roles of vinculin in cell–cell and cell–matrix adhesions. Emphasis is placed on the how vinculin is recruited, activated and regulated. We also highlight the recent understanding of how vinculin responds to and transmits force at integrin- and cadherin-containing adhesion complexes to the cytoskeleton. Furthermore, we discuss roles of vinculin in binding to and rearranging the actin cytoskeleton.

show abstract

Vinculin Regulates Assembly of Talin: β3 Integrin Complexes

Cited by 13 publications

References 45 publications

Computational and experimental analysis of bioactive peptide linear motifs in the integrin adhesome

Computational and experimental analysis of bioactive peptide linear motifs in the integrin adhesome

Microenvironmental Stiffness Regulates Dental Papilla Cell Differentiation: Implications for the Importance of Fibronectin–Paxillin−β-Catenin Axis

Vinculin in cell–cell and cell–matrix adhesions

Contact Info

Product

Resources

About